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Stochastic Binding of Ca(2+) Ions in the Dyadic Cleft; Continuous versus Random Walk Description of Diffusion

Ca(2+) signaling in the dyadic cleft in ventricular myocytes is fundamentally discrete and stochastic. We study the stochastic binding of single Ca(2+) ions to receptors in the cleft using two different models of diffusion: a stochastic and discrete Random Walk (RW) model, and a deterministic contin...

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Detalles Bibliográficos
Autores principales: Hake, Johan, Lines, Glenn T.
Formato: Texto
Lenguaje:English
Publicado: The Biophysical Society 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2480677/
https://www.ncbi.nlm.nih.gov/pubmed/18263662
http://dx.doi.org/10.1529/biophysj.106.103523
Descripción
Sumario:Ca(2+) signaling in the dyadic cleft in ventricular myocytes is fundamentally discrete and stochastic. We study the stochastic binding of single Ca(2+) ions to receptors in the cleft using two different models of diffusion: a stochastic and discrete Random Walk (RW) model, and a deterministic continuous model. We investigate whether the latter model, together with a stochastic receptor model, can reproduce binding events registered in fully stochastic RW simulations. By evaluating the continuous model goodness-of-fit for a large range of parameters, we present evidence that it can. Further, we show that the large fluctuations in binding rate observed at the level of single time-steps are integrated and smoothed at the larger timescale of binding events, which explains the continuous model goodness-of-fit. With these results we demonstrate that the stochasticity and discreteness of the Ca(2+) signaling in the dyadic cleft, determined by single binding events, can be described using a deterministic model of Ca(2+) diffusion together with a stochastic model of the binding events, for a specific range of physiological relevant parameters. Time-consuming RW simulations can thus be avoided. We also present a new analytical model of bimolecular binding probabilities, which we use in the RW simulations and the statistical analysis.